Study of Lemborexant for Irregular Sleep-Wake Rhythm Disorder and Mild to Moderate Alzheimer's Disease Dementia

NCT ID: NCT03001557

Last Updated: 2021-05-17

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

63 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-20

Study Completion Date

2020-04-17

Brief Summary

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This study will be conducted to determine the dose response of lemborexant (LEM) on the change from baseline in actigraphy-derived sleep-related parameters, wake-related parameters, and circadian-rhythm related parameters. Following the eligibility screening period, eligible participants will be assigned at random to 1 of 4 doses of LEM or to placebo for 4 weeks. After a 2-week follow-up period, eligible participants may enter an open-label extension period for up to 30 months or until the program discontinuation.

Detailed Description

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Conditions

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Irregular Sleep-Wake Rhythm Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Lemborexant 2.5 milligrams (mg)

Participants will take one lemborexant 2.5 mg tablet and one lemborexant-matched placebo tablet orally each night for 28 consecutive nights immediately (i.e., within 5 minutes) before the time the participant intends to try to sleep.

Group Type EXPERIMENTAL

Lemborexant 2.5 mg

Intervention Type DRUG

Lemborexant 2.5 mg tablets

Lemborexant-matched placebo

Intervention Type DRUG

Lemborexant-matched placebo tablets

Lemborexant 5 mg

Participants will take one lemborexant 5 mg tablet and one lemborexant-matched placebo tablet orally each night for 28 consecutive nights immediately (i.e., within 5 minutes) before the time the participant intends to try to sleep.

Group Type EXPERIMENTAL

Lemborexant 5 mg

Intervention Type DRUG

Lemborexant 5 mg tablets

Lemborexant-matched placebo

Intervention Type DRUG

Lemborexant-matched placebo tablets

Lemborexant 10 mg

Participants will take one lemborexant 10 mg tablet and one lemborexant-matched placebo tablet orally each night for 28 consecutive nights immediately (i.e., within 5 minutes) before the time the participant intends to try to sleep.

Group Type EXPERIMENTAL

Lemborexant 10 mg

Intervention Type DRUG

Lemborexant 10 mg tablets

Lemborexant-matched placebo

Intervention Type DRUG

Lemborexant-matched placebo tablets

Lemborexant 15 mg

Participants will take one lemborexant 5 mg tablet and one lemborexant 10 mg tablet orally each night for 28 consecutive nights immediately (i.e., within 5 minutes) before the time the participant intends to try to sleep.

Group Type EXPERIMENTAL

Lemborexant 10 mg

Intervention Type DRUG

Lemborexant 10 mg tablets

Lemborexant 15 mg

Intervention Type DRUG

Lemborexant 5 mg and 10 mg tablets

Lemborexant-matched placebo

Participants will take two lemborexant-matched placebo tablets orally each night for 28 consecutive nights immediately (i.e., within 5 minutes) before the time the participant intends to try to sleep.

Group Type PLACEBO_COMPARATOR

Lemborexant-matched placebo

Intervention Type DRUG

Lemborexant-matched placebo tablets

Interventions

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Lemborexant 2.5 mg

Lemborexant 2.5 mg tablets

Intervention Type DRUG

Lemborexant 5 mg

Lemborexant 5 mg tablets

Intervention Type DRUG

Lemborexant 10 mg

Lemborexant 10 mg tablets

Intervention Type DRUG

Lemborexant 15 mg

Lemborexant 5 mg and 10 mg tablets

Intervention Type DRUG

Lemborexant-matched placebo

Lemborexant-matched placebo tablets

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Male or female, age 60 to 90 years at the time of informed consent
* Able to provide informed consent. If a participant lacks capacity to consent in the investigator's opinion, the participant's assent should be obtained, if required in accordance with local laws, regulations and customs, and the written informed consent of a legal representative should be obtained (capacity to consent and definition of legal representative should be determined in accordance with applicable local laws and regulations).
* Documentation of diagnosis with Alzheimer's disease dementia (AD-D) on the basis of the National Institute on Aging/Alzheimer's Association Diagnostic Guidelines
* Mini Mental State Examination 10 to 26 at Screening
* Meets criteria for Circadian Rhythm Sleep Disorder, Irregular Sleep-Wake Type (Diagnostic and Statistical Manual of Mental Disorders - 5th edition) and the 10th revision of the International Classification of Diseases, as follows: Complaint by the participant or caregiver of difficulty sleeping during the night and/or excessive daytime sleepiness associated with multiple irregular sleep bouts during a 24-hour period
* Frequency of complaint of sleep and wake fragmentation ≥3 days per week
* Duration of complaint of sleep and wake fragmentation ≥3 months
* During the Screening Period, mean actigraphy-derived sleep efficiency (aSE) \<87.5% within the defined nocturnal sleep period and mean actigraphy-derived wake efficiency (aWE) \<87.5% during the defined wake period
* Confirmation by actigraphy of a combination of sleep bouts of \>10 minutes during the wake period plus wake bouts of \>10 minutes during the sleep period, totaling at least 4 bouts per 24 hours period, ≥ 3 days per week
* Ambulatory and living in the community or in a residence not classified as a skilled nursing facility (an assisted living facility with separate living quarters where participants and their caregivers reside is acceptable)
* Willing not to start a behavioral or other treatment program for sleep or wake difficulties and not to start a new treatment for other symptoms of AD-D during participation in the study
* Has a reliable and competent caregiver (or caregiver and informants) who can accompany the participant to study visits, administer study medication on a nightly basis and provide information on the status of the participant
* For participants taking a cholinesterase inhibitor and/or memantine, dosing regimen must have been stable for at least 3 months


* Completed the Core Study (End of Study \[EOS\] Visit). Participants who participated in the Core Study and completed the EOS Visit within 30 days may return to participate in the Extension Phase as long as there are no contraindications due to ongoing adverse events or prohibited medications.


* Able to provide informed consent
* Spends at least 10 hours per week with the participant
* Able to meet caregiver requirements
* Willing to provide information on himself/herself regarding sleep quality and caregiver Burden

Exclusion Criteria

* A diagnosis of vascular dementia, dementia following multiple strokes, or any synucleinopathy / Lewy body disorder. This includes Dementia with Lewy Bodies and Parkinson's disease with or without dementia.
* A current diagnosis of moderate to severe obstructive sleep apnea (OSA) or central sleep apnea, or current use of continuous positive airways pressure even if mild severity of OSA, restless legs syndrome, periodic limb movement disorder (with awakenings), or narcolepsy
* An Apnea-Hypopnea Index or equivalent ≥15 events/hour on diagnostic sleep study conducted prior to Baseline or within 6 months of Screening
* A clinically significant movement disorder that would affect the differentiation of sleep and wake by the actigraphy analytic algorithm
* Current symptoms or history during the past year of Rapid Eye Movement Behavior Disorder or sleep-related violent behavior
* Probable Major Depression, as evidenced by score \>10 on the Cornell Scale for Depression in Dementia at Screening
* Unable to tolerate wearing the actigraph. At a minimum, participants must be able to wear the actigraph for 5 complete days out of 7 days' data. A day will be considered complete as long as data from 90% of the 24-hour period are able to be scored.
* Excessive caffeine use that in the opinion of the investigator contributes to the participant's Irregular Sleep-Wake Rhythm Disorder (ISWRD)
* History of drug or alcohol dependency or abuse within approximately the previous 2 years
* Reports habitually consuming more than 14 drinks containing alcohol per week or habitually consumes alcohol within 3 hours before bedtime and unwilling to limit alcohol intake to 2 or fewer drinks per day or forego having alcohol within 3 hours before bedtime for the duration of his/her participation in the study
* Known to be human immunodeficiency virus positive
* Active viral hepatitis (B or C) as demonstrated by positive serology at Screening
* A prolonged QTcF interval (QTcF \>450 milliseconds\[ms\]) as demonstrated by a repeated electrocardiogram (ECG) at Screening (repeated only if initial ECG indicates a QTcF interval \>450 ms) (participants with evidence of bundle branch block are not excluded if the block is not clinically significant, as documented by the investigator in the source document)
* Current evidence of clinically significant disease that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments
* Any history of a medical or psychiatric condition other than Alzheimer's Disease dementia that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments
* History of malignancy within the previous 5 years except for adequately treated basal cell or squamous cell skin cancer or cervical carcinoma in situ
* Any suicidal ideation with intent with or without a plan, at the time of or within 6 months of Screening, as indicated by answering "Yes" to questions 4 and 5 on the Suicidal Ideation section of the electronic version of the Columbia Suicide Severity Rating Scale (eC-SSRS)
* Any suicidal behavior within the past 10 years based on the eC-SSRS
* History of violence toward the caregiver or others
* Scheduled for surgery using general anesthesia during the study
* Used any prohibited prescription or over-the-counter concomitant medications within 1 week or 5 half-lives, whichever is longer, before starting actigraphy during Screening
* Used any modality of treatment for ISWRD between Screening and Randomization based on approaches related to circadian rhythms, including phototherapy (light therapy), melatonin and melatonin agonists
* Failed treatment with Belsomra (efficacy and/or safety) following treatment with an appropriate dose and of adequate duration in the opinion of the investigator
* Transmeridian travel across more than 3 time zones between Screening and Randomization, or plans to travel across more than 3 time zones during the study
* Hypersensitivity to lemborexant or to its excipients
* Currently enrolled in another clinical trial, except for observational studies with no treatment component
* Used any investigational drug or device before informed consent (ie, within 30 days or 5× the investigational drug half-life whichever is longer or 6 months for potential disease-modifying drugs)
* Previously participated in any clinical trial of lemborexant
Minimum Eligible Age

60 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Purdue Pharma LP

INDUSTRY

Sponsor Role collaborator

Eisai Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Facility #1

Little Rock, Arkansas, United States

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Rogers, Arkansas, United States

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Costa Mesa, California, United States

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Fullerton, California, United States

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Glendale, California, United States

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Irvine, California, United States

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Irvine, California, United States

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La Jolla, California, United States

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San Diego, California, United States

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Santa Monica, California, United States

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Bradenton, Florida, United States

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Brandon, Florida, United States

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Brooksville, Florida, United States

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Hallandale, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami Lakes, Florida, United States

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Miami Springs, Florida, United States

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Orlando, Florida, United States

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Orlando, Florida, United States

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Sunrise, Florida, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Columbus, Georgia, United States

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Macon, Georgia, United States

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Wichita, Kansas, United States

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Belmont, Massachusetts, United States

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Nevada Senior Services (NSS) Adult Day Care Center

Henderson, Nevada, United States

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Las Vegas, Nevada, United States

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Toms River, New Jersey, United States

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Toms River, New Jersey, United States

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Charlotte, North Carolina, United States

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Durham, North Carolina, United States

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Raleigh, North Carolina, United States

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Norristown, Pennsylvania, United States

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Willow Grove, Pennsylvania, United States

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Columbia, South Carolina, United States

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Eisai Trial Site #1

Nagoya, Aichi-ken, Japan

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Eisai Trial Site #1

Fujisawa, Kanagawa, Japan

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Eisai Trial Site #1

Kawasaki-shi, Kanagawa, Japan

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Eisai Trial Site #1

Wako, Saitama, Japan

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Eisai Trial Site #1

Kodaira, Tokyo, Japan

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Eisai Trial Site #1

Setagaya City, Tokyo, Japan

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Eisai Trial Site #1

Shinjuku, Tokyo, Japan

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Eisai Trial Site #1

Tachikawa-shi, Tokyo, Japan

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Brighton and Sussex Medical School

Brighton, East Sussex, United Kingdom

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Cognitive Treatment and Research Unit

Crowborough, East Sussex, United Kingdom

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University of Edinburgh - PPDS

Edinburgh, , United Kingdom

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Countries

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United States Japan United Kingdom

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan: Core Phase

View Document

Document Type: Statistical Analysis Plan: Extension Phase

View Document

Other Identifiers

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2017-003306-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

E2006-G000-202

Identifier Type: -

Identifier Source: org_study_id

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